3-191329975-AGTAG-A

Variant names:

• chr3-191329975-AGTAG-A
• rs10580681
• NM_178335.3:c.49+255_49+258delAGGT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_178335.3(CCDC50):​c.49+255_49+258delAGGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 144,054 control chromosomes in the GnomAD database, including 4,770 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4770 hom., cov: 21)
• Consequence: CCDC50 NM_178335.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00
• Publications: 0 publications found

Genes affected

CCDC50 (HGNC:18111): (coiled-coil domain containing 50) This gene encodes a soluble, cytoplasmic, tyrosine-phosphorylated protein with multiple ubiquitin-interacting domains. Mutations in this gene cause nonsyndromic, postlingual, progressive sensorineural DFNA44 hearing loss. In mouse, the protein is expressed in the inner ear during development and postnatal maturation and associates with microtubule-based structures. This protein may also function as a negative regulator of NF-kB signaling and as an effector of epidermal growth factor (EGF)-mediated cell signaling. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]

UTS2B (HGNC:30894): (urotensin 2B) Predicted to enable G protein-coupled receptor binding activity. Predicted to be involved in regulation of blood pressure. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-191329975-AGTAG-A is Benign according to our data. Variant chr3-191329975-AGTAG-A is described in ClinVar as Benign. ClinVar VariationId is 1230089.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178335.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC50	NM_178335.3	MANE Select	c.49+255_49+258delAGGT		intron	N/A	NP_848018.1	Q8IVM0-2
	UTS2B	NM_198152.5	MANE Select	c.-665+435_-665+438delCTAC		intron	N/A	NP_937795.2	Q765I0
	CCDC50	NM_174908.4		c.49+255_49+258delAGGT		intron	N/A	NP_777568.1	Q8IVM0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC50	ENST00000392455.9	TSL:1 MANE Select	c.49+253_49+256delGTAG		intron	N/A	ENSP00000376249.4	Q8IVM0-2
	UTS2B	ENST00000340524.10	TSL:2 MANE Select	c.-665+435_-665+438delCTAC		intron	N/A	ENSP00000340526.5	Q765I0
	CCDC50	ENST00000392456.4	TSL:1	c.49+253_49+256delGTAG		intron	N/A	ENSP00000376250.4	Q8IVM0-1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 32548 AN: 143950 Hom.: 4764 Cov.: 21

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.216

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.226 AC: 32574 AN: 144054 Hom.: 4770 Cov.: 21 AF XY: 0.233 AC XY: 16187 AN XY: 69478

African (AFR) AF: 0.188 AC: 7410 AN: 39342

American (AMR) AF: 0.278 AC: 3965 AN: 14282

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 715 AN: 3404

East Asian (EAS) AF: 0.670 AC: 3094 AN: 4618

South Asian (SAS) AF: 0.422 AC: 1825 AN: 4322

European-Finnish (FIN) AF: 0.205 AC: 1788 AN: 8718

Middle Eastern (MID) AF: 0.283 AC: 77 AN: 272

European-Non Finnish (NFE) AF: 0.199 AC: 13159 AN: 66230

Other (OTH) AF: 0.221 AC: 437 AN: 1980

Alfa AF: 0.217 Hom.: 443

Bravo AF: 0.239

Asia WGS AF: 0.497 AC: 1653 AN: 3340

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10580681; hg19: chr3-191047764;